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Non-alcoholic steatohepatitis (NASH) is characterized from its early stages by a profound remodeling of the liver microenvironment, encompassing changes in the composition and activities of multiple cell types and associated gene expression patterns. Hyperpolarized (HP) 13C MRI provides a unique view of the metabolic microenvironment, with potential relevance for early diagnosis of liver disease. Previous studies have detected changes in HP 13C pyruvate to lactate conversion, catalyzed by lactate dehydrogenase (LDH), with experimental liver injury. HP ∝ -ketobutyrate (∝ KB) is a close molecular analog of pyruvate with modified specificity for LDH isoforms, specifically attenuated activity with their LDHA-expressed subunits that dominate liver parenchyma. Building on recent results with pyruvate, we investigated HP ∝ KB in methionine-choline deficient (MCD) diet as a model of early-stage NASH. Similarity of results between this new agent and pyruvate (~ 50% drop in cytoplasmic reducing capacity), interpreted together with gene expression data from the model, suggests that changes are mediated through broad effects on intermediary metabolism. Plausible mechanisms are depletion of the lactate pool by upregulation of gluconeogenesis (GNG) and pentose phosphate pathway (PPP) flux, and a possible shift toward increased lactate oxidation. These changes may reflect high levels of oxidative stress and/or shifting macrophage populations in NASH. [ABSTRACT FROM AUTHOR]

Purpose: Non-invasive imaging is a key clinical tool for detection and treatment monitoring of infections. Existing clinical imaging techniques are frequently unable to distinguish infection from tumors or sterile inflammation. This challenge is well-illustrated by prosthetic joint infections that often complicate joint replacements. D-methyl-11C-methionine (D-11C-Met) is a new bacteria-specific PET radiotracer, based on an amino acid D-enantiomer, that is rapidly incorporated into the bacterial cell wall. In this manuscript, we describe the biodistribution, radiation dosimetry, and initial human experience using D-11C-Met in patients with suspected prosthetic joint infections. Methods: 614.5 ± 100.2 MBq of D-11C-Met was synthesized using an automated in-loop radiosynthesis method and administered to six healthy volunteers and five patients with suspected prosthetic joint infection, who were studied by PET/MRI. Time-activity curves were used to calculate residence times for each source organ. Absorbed doses to each organ and body effective doses were calculated using OLINDA/EXM 1.1 with both ICRP 60 and ICRP 103 tissue weighting factors. SUVmax and SUVpeak were calculated for volumes of interest (VOIs) in joints with suspected infection, the unaffected contralateral joint, blood pool, and soft tissue background. A two-tissue compartment model was used for kinetic modeling. Results: D-11C-Met was well tolerated in all subjects. The tracer showed clearance from both urinary (rapid) and hepatobiliary (slow) pathways as well as low effective doses. Moreover, minimal background was observed in both organs with resident micro-flora and target organs, such as the spine and musculoskeletal system. Additionally, D-11C-Met showed increased focal uptake in areas of suspected infection, demonstrated by a significantly higher SUVmax and SUVpeak calculated from VOIs of joints with suspected infections compared to the contralateral joints, blood pool, and background (P < 0.01). Furthermore, higher distribution volume and binding potential were observed in suspected infections compared to the unaffected joints. Conclusion: D-11C-Met has a favorable radiation profile, minimal background uptake, and fast urinary extraction. Furthermore, D-11C-Met showed increased uptake in areas of suspected infection, making this a promising approach. Validation in larger clinical trials with a rigorous gold standard is still required. [ABSTRACT FROM AUTHOR]

In this case report, dual-energy CT was critical in the diagnosis of acute mesenteric ischemia by differentiating normal contrast-enhanced bowel and hemorrhagic necrosis. Iodine map showed a segment of small bowel with minimal contrast enhancement, and virtual non-contrast imaging revealed hyperattenuating bowel. This finding changed management for the patient and prevented complications from impending bowel perforation. Histopathological analysis confirmed hemorrhagic necrosis of the bowel segment. In cases of suspected bowel ischemia, dual-energy CT can distinguish bowel wall hemorrhage from contrast enhancement and allow for accurate diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: Determine whether liver attenuation measured on dual-energy CT (DECT) virtual non-contrast examinations predicts the presence of fatty liver. Methods: Single-institution retrospective review from 2016 to 2020 found patients with DECT and proton density fat fraction MRI (MRI PDFF) within 30 days. MRI PDFF was the reference standard for determining hepatic steatosis. Attenuation measurements from VNC and mixed 120 kVp-like images were compared to MRI PDFF in the right and left lobes. Performance of VNC was compared to measurement of the liver-spleen attenuation difference (LSAD). Results: 128 patients were included (69 men, 59 women) with mean age 51.6 years (range 14–98 years). > 90% of patients received CT and MRI in the emergency department or as inpatients. Median interval between DECT and MRI PDFF was 2 days (range 0–28 days). Prevalence of fatty liver using the reference standard (MRI PDFF > 6%) was 24%. Pearson correlation coefficient between VNC and MRI- DFF was -0.64 (right) and -0.68 (left, both p < 0.0001). For LSAD, correlation was − 0.43 in both lobes (p < 0.0001). Considering MRI PDFF > 6% as diagnostic of steatosis, area under the receiver operator characteristic curve (AUC) was 0.834 and 0.872 in the right and left hepatic lobes, with an optimal threshold of 54.8 HU (right) and 52.5 HU (left), yielding sensitivity/specificity of 57%/93.9% (right) and 67.9%/90% (left). For LSAD, AUC was 0.808 (right) and 0.767 (left) with optimal sensitivity/specificity of 93.3%/57.1% (right) and 78.6%/68% (left). Conclusion: Attenuation measured at VNC CT was moderately correlated with liver fat content and had > 90% specificity for diagnosis of fatty liver. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate correlation of "placental bulge sign" with myometrial invasion in placenta accreta spectrum (PAS) disorders. Placental bulge is defined as deviation of external uterine contour from expected plane caused by abnormal outward bulge of placental tissue. Materials and methods: In this IRB-approved, retrospective study, all patients undergoing MRI for PAS disorders between March 2014 and 2018 were included. Patients who delivered elsewhere were excluded. Imaging was reviewed by 2 independent readers. Surgical pathology from Cesarean hysterectomy or pathology of the delivered placenta was used as reference standard. Fisher's exact and kappa tests were used for statistical analysis. Results: Sixty-one patients underwent MRI for PAS disorders. Two excluded patients delivered elsewhere. Placental bulge was present in 32 of 34 cases with myometrial invasion [True positive 32/34 = 94% (95% CI 0.80–0.99)]. Placental bulge was absent in 24 of 25 cases of normal placenta or placenta accreta without myometrial invasion [True negative = 24/25, 96% (95% CI 80–99.8%)]. Positive and negative predictive values were 97% and 96%, respectively. Placental bulge in conjunction with other findings of PAS disorder was 100% indicative of myometrial invasion (p < 0.01). Kappa value of 0.87 signified excellent inter-reader concordance. In 1 false positive, placenta itself was normal but the bulge was present. Surgical pathology revealed markedly thinned, fibrotic myometrium without accreta. One false-negative case was imaged at 16 weeks and may have been imaged too early. Conclusions: Placental bulge in conjunction with other findings of invasive placenta is 100% predictive of myometrial invasion. Using the bulge alone without other signs can lead to false-positive results. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate acquisition time and clinical image quality of a variable refocusing flip angle (vrf) single-shot fast spin echo (SSFSE) sequence in comparison with a conventional SSFSE sequence for imaging of liver lesions in patients undergoing whole-body PET/MRI for oncologic staging.Methods: A vrfSSFSE sequence was acquired in 43 patients with known pancreatic neuroendocrine tumors undergoing 68Ga-DOTA-TOC PET on a simultaneous time-of-flight 3.0T PET/MRI. Liver lesions ≥1.5 cm with radionucleotide uptake were analyzed. Contrast-to-noise ratios (CNRs) were measured, and four blinded radiologists assessed overall image quality. Differences in repetition time and CNR were assessed using a paired Student’s t test with p < 0.05 considered statistically significant. Inter-reader variability was assessed with Fleiss’ kappa statistic.Results: 53 eligible lesions in 27 patients were included for analysis. vrfSSFSE demonstrated higher mean lesion CNR compared to SSFSE (9.9 ± 4.1 vs. 6.7 ± 4.1, p < 0.001). Mean repetition time (TR) was 679 ± 97 ms for the vrfSSFSE sequence compared to 1139 ± 106 ms for SSFSE (p < 0.0001), corresponding to a 1.7-fold decrease in acquisition time. Overall quality of liver lesion and common bile duct images with the vrfSSFSE sequence was graded as superior than or equivalent to the SSFSE sequence for 59% and 67% of patients, respectively.Conclusions: Compared to conventional SSFSE, vrfSSFSE resulted in improved lesion contrast on simultaneous PET/MRI in patients with liver metastases. Due to decreased SAR demands, vrfSSFSE significantly decreased TR, allowing coverage of the entire liver in a single twenty-second breath hold. This may have important clinical implications in the setting of PET/MRI, where scan time is limited by the necessity of whole-body image acquisition in addition to bed specific imaging. [ABSTRACT FROM AUTHOR]

Purposes: To assess the ability of a single isotropic 3D T2 FSE sequence to identify the normal appendix in children with potential implication as alternative second-line modality in pediatric appendicitis.Materials and Methods: Retrospective review of MR abdomino-pelvis or pelvis in children from Oct 2014-Dec 2016 was done. Only exams with 3D T2 FSE sequence performed on a single scanner type were selected. Patients with history of post appendectomy, studies in which field of view did not include ileocecal valve, with technical and protocol errors, or with fat-saturated acquisition were excluded. All images were blindly reviewed by three radiologists. The following questions were asked: (1) Is the appendix visualized?, (2) What is the most clearly demonstrable plane?, (3) Where is the appendix located?, (4) Are there any findings indicating appendicitis? Average pairwise percentage and Fleiss Kappa were used to assess the inter-rater agreement on the visualization and location of the appendix.Results: A total of 22 MRI studies were reviewed (F = 13:M = 9, Mean age = 11.45 yrs. [SD = 4.3]). Total MRI scan time was estimated at 6 mins. Readers saw appendix in 72.7-81.8%, and saw with high confidence in 12 cases (54.5%), low confidence in 4-6 case (18.2-27.3%), and did not see in 4-6 cases(18.2-27.3%). The average pairwise percentage agreement was 71.2%. Fleiss Kappa of overall rating of visualization was 0.52 (p < 0.001). Fleiss Kappa of high confidence of visualization was 0.76 (p < 0.001). Reader 1 and reader 2 saw the appendix best on the axial plane. Reader 3 saw the appendix best on the coronal plane. For location, deep pelvis was the most common identified location. The average pairwise percentage agreement was 68.2% and Fleiss Kappa was 0.76 (p < 0.001). There is no findings indicating appendicitis.Conclusion: A single 3D T2 FSE sequence had good ability to detect normal appendices and also allowed multiplanar reconstructions, which may use as a single-sequence protocol in cases of suspected appendicitis in children when ultrasound is inconclusive. [ABSTRACT FROM AUTHOR]

Hepatic fibrosis is potentially reversible; however early diagnosis is necessary for treatment in order to halt progression to cirrhosis and development of complications including portal hypertension and hepatocellular carcinoma. Morphologic signs of cirrhosis on ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) alone are unreliable and are seen with more advanced disease. Newer imaging techniques to diagnose liver fibrosis are reliable and accurate, and include magnetic resonance elastography and US elastography (one-dimensional transient elastography and point shear wave elastography or acoustic radiation force impulse imaging). Research is ongoing with multiple other techniques for the noninvasive diagnosis of hepatic fibrosis, including MRI with diffusion-weighted imaging, hepatobiliary contrast enhancement, and perfusion; CT using perfusion, fractional extracellular space techniques, and dual-energy, contrast-enhanced US, texture analysis in multiple modalities, quantitative mapping, and direct molecular imaging probes. Efforts to advance the noninvasive imaging assessment of hepatic fibrosis will facilitate earlier diagnosis and improve patient monitoring with the goal of preventing the progression to cirrhosis and its complications. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the reduction of out-of-field artifacts caused by body parts outside the field of view (FOV) at rapid kVp switching dual-energy CT (rsDECT). Materials and methods: This retrospective study was approved by our institutional review board. Informed consent was not required. We viewed 246 consecutive rsDECT thoracoabdominal scans to identify those with body parts outside the maximal FOV of 50 cm. The maximal length, thickness, and subjective severity of the out-of-field artifacts were recorded for the 40, 65, and 140 keV virtual monochromatic and iodine and water density images. Artifact severity was rated on a 6-point scale from 0 = absent to 5 = obscures intraabdominal/intrathoracic anatomic detail. Artifact thickness and severity scores were compared by t-test and Wilcoxon tests, respectively. Results: In 20 of 246 scans (8.1%), body parts extended past the maximum FOV of 50 cm. The mean BMI of these 20 patients was 40.2 kg/m (range, 26.83-61.69 kg/m), and out-of-field artifacts occurred for all 20. The mean out-of-field artifact maximal length was 16.6 cm. The mean artifact thickness was significantly less for iodine density (0.6 mm) than for the 65 keV and water density images (8.4 and 13.5 mm, respectively, p < 0.001 each comparison). The mean artifact severity score was lower for iodine density (0.2) than for the 65 keV and water density images (2.5 and 2.6, respectively, p < 0.001 each). Conclusion: Iodine density images reduce out-of-field image artifact at rsDECT and assists in the evaluation of peripheral tissues that extend beyond the maximal CT FOV. [ABSTRACT FROM AUTHOR]

Purpose: Locoregional therapies for hepatocellular carcinoma (HCC) offer alternatives for patients unable to undergo resection or awaiting transplant. We sought to evaluate the prevalence and interobserver agreement of imaging features suggestive of viable tumor at posttherapy CT/MRI and to determine a size threshold for tumor detection. Methods: Patients having undergone liver transplant or hepatectomy between 2012 and 2014 with presurgical embolization or ablation of HCC were identified. Imaging was retrospectively reviewed, and enhancement characteristics of each lesion were noted by two radiologists. Original pathology slides were reviewed, and the size of nodular viable tumor was noted, if present. Cohen's kappa was used to evaluate interobserver agreement. Results: 87 patients with 129 HCCs were reviewed retrospectively following IRB approval. 50% (65/129) of lesions showed viable tumor at pathology. 86 lesions (67%) were imaged with CT and 43 (33%) with MR. Of viable lesions, 25 (38%) showed nodular arterial enhancement and 18 (28%) demonstrated washout. One lesion had capsule appearance. Sensitivity/specificity for nodular enhancement, washout, and capsule were 0.38/0.83, 0.28/0.89, and 0.02/1.00, respectively. Overall detection rate was 41% of <1 cm, 54% of 1-2 cm, and 57% of >2 cm viable lesions. Conclusions: Nodular arterial enhancement was most frequently observed, followed by washout. Both showed moderate interobserver agreement. Sensitivity of any imaging feature was less than 50%, though findings were specific for viable disease. There is limited detection of nodules of viable tumor <1 cm and only marginal detection of larger lesions, though MRI outperformed CT for the detection of subcentimeter viable tumor [ABSTRACT FROM AUTHOR]

Parallel magnetic resonance imaging (MRI) techniques use spatial information from arrays of radiofrequency (RF) detector coils to accelerate imaging. A number of parallel MRI techniques have been described in recent years, and numerous clinical applications are currently being explored. The advent of practical parallel imaging presents various challenges for image reconstruction and RF system design. Recent advances in tailored SiMultaneous Acquisition of Spatial Harmonics (SMASH) image reconstructions are summarized. These advances enable robust SMASH imaging in arbitrary image planes with a wide range of coil array geometries. A generalized formalism is described which may be used to understand the relations between SMASH and SENSE, to derive typical implementations of each as special cases, and to form hybrid techniques combining some of the advantages of both. Accurate knowledge of coil sensitivities is crucial for parallel MRI, and errors in calibration represent one of the most common and the most pernicious sources of error in parallel image reconstructions. As one example, motion of the patient and or the coil array between the sensitivity reference scan and the accelerated acquisition can lead to calibration errors and reconstruction artifacts. Self-calibrating parallel MRI approaches that address this problem by eliminating the need for external sensitivity references are reviewed. The ultimate achievable signal-to-noise ratio (SNR) for parallel MRI studies is closely tied to the geometry and sensitivity patterns of the coil arrays used for spatial encoding. Several parallel imaging array designs that depart from the traditional model of overlapped adjacent loop elements are described. [ABSTRACT FROM AUTHOR]

To determine the structure of three nuclear localizing lupus anti-DNA immunoglobulins (Igs) and to search for clues to mechanisms of cellular and/or nuclear access, their H- and L-chain variable region sequences were determined and subjected to three-dimensional modeling. Although the results indicate heterogeneity in their primary structures, the H chains are encoded by 3 members of the J558 V gene family with a common tertiary conformation that is not shared by a J558-encoded nonnuclear localizing anti-DNA control Ig. Furthermore, at least two of the Igs share a conformational motif in the H-chain CDR3, and all three Igs contain multiple positively charged amino acids in their CDRs, resembling nuclear localization signals that direct protein nuclear import. Notably, each V and V gene is also found recurrently among previously described autoantibodies. Molecular analysis further indicates that both germline-encoded and significantly mutated V genes can generate nuclear localizing anti-DNA Ig. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) has become highly prevalent, now considered the most common liver disease in the western world. Approximately one-third of patients with NASH develop non-alchoholic steatohepatitis (NASH), histologically defined by lobular and portal inflammation, and accompanied by marked oxidative stress. Patients with NASH are at increased risk for cirrhosis and hepatocellular carcinoma, and diagnosis currently requires invasive biopsy. In animal models of NASH, particularly the methionine-choline deficient (MCD) model, profound changes are seen in redox enzymes and key intracellular antioxidants. To study antioxidant status in NASH non-invasively, we applied the redox probe hyperpolarized [1-13C] dehydroascorbic acid (HP DHA), which is reduced to Vitamin C (VitC) rapidly in the normal liver. In MCD mice, we observed a significant decrease in HP DHA to VitC conversion that accompanied hepatic fat deposition. When these animals were subsequently placed on a normal diet, resonance ratios reverted to those seen in control mice. These findings suggest that HP DHA, a potentially clinically translatable imaging agent, holds special promise in imaging NASH and other metabolic syndromes, to monitor disease progression and response to targeted therapies. [ABSTRACT FROM AUTHOR]